Apolipoprotein A-I and adenosine triphosphate-binding cassette transporter A1 expression alleviates lipid accumulation in hepatocytes
Apolipoprotein A-I and adenosine triphosphate-binding cassette transporter A1 expression alleviates lipid accumulation in hepatocytes
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DOI：
10.1111/jgh.12430
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发表时间：
2014-03-01
影响因子：
4.1
通讯作者：
Wang, Yutong
中科院分区：
文献类型：
--
作者：
Liu, Wei;Qin, Ling;Wang, Yutong
背景与目的脂质代谢异常可能参与非酒精性脂肪性肝炎的发病机制。ATP结合盒转运蛋白A1（ABCA 1）介导胆固醇和磷脂从细胞转运到高密度脂蛋白载脂蛋白。ABCA 1对载脂蛋白A-I（apoA-I）的脂化是胆固醇逆向转运和血浆高密度脂蛋白生成的限速步骤。在这里，我们检测了apoA-I或ABCA 1过表达对BEL-7402细胞中肝脂质水平的影响。方法通过转染在BEL-7402细胞中过表达人ABCA 1或apoA-I，并通过腺病毒载体在MCD饮食的C57 BL/6 J小鼠中过表达人apoA-I。I或ABCA 1导致胆固醇流出增加，细胞脂肪酸和甘油三酯减少。然而，ABCA 1的siRNA抑制后，apoA-I的过表达未能降低细胞脂肪酸和甘油三酯。ApoA-I或ABCA 1过表达也导致内质网应激相关蛋白GRP 78和SREBP-1表达减少。apoA-I在小鼠中的过表达也降低了肝脏脂质levels.ConclusionsExpression的apoA-I或ABCA 1可以减少脂肪变性通过减少脂质储存在肝细胞通过脂质转运，也可能减少内质网应激，进一步减轻肝脂肪变性。
Background and AimAbnormal lipid metabolism may contribute to the pathogenesis of non-alcoholic steatohepatitis. ATP-binding cassette transporter A1 (ABCA1) mediates the transport of cholesterol and phospholipids from cells to high density lipoprotein apolipoproteins. The lipidation of apolipoprotein A-I (apoA-I) by ABCA1 is the rate-limiting step in reverse cholesterol transport and the generation of plasma high density lipoprotein. Here, we examined the effect of apoA-I or ABCA1 overexpression on hepatic lipid levels in BEL-7402 cells.MethodsHuman ABCA1 or apoA-I was overexpressed in BEL-7402 hepatocytes by transfection and human apoA-I was overexpressed via adenoviral vector in C57BL/6J mice with MCD diet.ResultsOverexpression of either apoA-I or ABCA1 resulted in an increase in cholesterol efflux and a decrease in cellular fatty acids and triglycerides. However, after repression of ABCA1 by its siRNA, overexpression of apoA-I failed to decrease both cellular fatty acids and triglycerides. ApoA-I or ABCA1 overexpression also resulted in a decrease in the expression of the endoplasmic reticulum stress-related proteins GRP78 and SREBP-1. Overexpression of apoA-I in mice also reduced hepatic lipid levels.ConclusionsExpression of apoA-I or ABCA1 can reduce steatosis by decreasing lipid storage in hepatocytes through lipid transport and may also reduce endoplasmic reticulum stress, further lessening hepatic steatosis.